ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.11241C>A (p.Tyr3747Ter) (rs777465132)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel, RCV000710334 SCV000840528 pathogenic Usher syndrome 2018-09-17 reviewed by expert panel curation The p.Tyr3747X variant in USH2A is predicted to cause a premature stop codon in biologically-relevant-exon 58/72 that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism (PVS1). The allele frequency of the p.Tyr3747X variant in the Ush2A gene is 0.017% (4/24020) of African chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org), which is a low enough frequency to award PM2_Supporting based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss ( PM2_Supporting). This variant has been detected in 1 patient with hearing loss in trans with a suspected pathogenic variant (PM3_Supporting, Partners LMM internal data SCV000713838.1). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied: PVS1, PM2_Supporting, PM3_Supporting.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000605356 SCV000713838 pathogenic Rare genetic deafness 2018-01-30 criteria provided, single submitter clinical testing The p.Tyr3747X variant in USH2A has not been previously reported in individuals with hearing loss or Usher syndrome, but has been identified in 0.02% (4/24020) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad .broadinstitute.org; dbSNP rs777465132). This nonsense variant leads to a premat ure termination codon at position 3747, which is predicted to lead to a truncate d or absent protein. Variants in USH2A resulting in a loss of function of the pr otein is an established disease mechanism in autosomal recessive Usher syndrome. In addition, this variant is likely in trans with the deletion of exons 63-64 i n USH2A given that previous cases with the deletion did not carry this variant. This provides additional evidence that the variant is pathogenic. In summary, th is variant meets our criteria to be classified as pathogenic for autosomal reces sive Usher syndrome. ACMG/AMP Criteria applied: PVS1; PM2; PM3.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.